| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pulmonary Fibrosis_Interstitial Lung Disease v0.201 | POT1 |
Zornitza Stark gene: POT1 was added gene: POT1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: POT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: POT1 were set to 35420632; 30995915 Phenotypes for gene: POT1 were set to Telomere syndrome, MONDO:0100137, POT1-related Review for gene: POT1 was set to AMBER Added comment: PMID 30995915 reports one individual with a heterozygous POT1 p.Q301H missense variant and adult‑onset progressive pulmonary fibrosis. PMID 35420632 reports 4 individuals from another unrelated family with a heterozygous POT1 p.L259S missense variant and adult‑onset idiopathic pulmonary fibrosis; the variant co‑segregates across two generations, shows genetic anticipation, and functional assays demonstrate loss‑of‑function. Telomere biology disorder. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.196 | NDUFAF6 |
Zornitza Stark gene: NDUFAF6 was added gene: NDUFAF6 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature founder tags were added to gene: NDUFAF6. Mode of inheritance for gene: NDUFAF6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFAF6 were set to 27466185 Phenotypes for gene: NDUFAF6 were set to Fanconi renotubular syndrome 5, MIM# 618913 Review for gene: NDUFAF6 was set to AMBER Added comment: PMID 27466185 reports 12 individuals from 8 unrelated families with biallelic intronic NDUFAF6 variants presenting with Acadian variant of Fanconi syndrome (renal Fanconi syndrome from birth, progressive chronic kidney disease, pulmonary interstitial fibrosis). Supportive functional data. Founder variant. No evidence other variants in this gene cause a lung phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.193 | MMACHC |
Zornitza Stark gene: MMACHC was added gene: MMACHC was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMACHC were set to 33231183; 32293809 Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type, MIM#277400 Review for gene: MMACHC was set to GREEN Added comment: PMID 32293809 reports four unrelated families and PMID 33231183 reports one unrelated family with MMACHC variants presenting with childhood‑onset diffuse interstitial lung disease, alveolar hemorrhage, pulmonary microangiopathy and pulmonary arterial hypertension; PMID 31969166 adds five additional individuals with MMACHC variants and interstitial lung disease. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.191 | LAMP3 |
Zornitza Stark gene: LAMP3 was added gene: LAMP3 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: LAMP3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LAMP3 were set to 40023045; 34161347 Phenotypes for gene: LAMP3 were set to Interstitial lung disease, MONDO:0015925, LAMP3-related Review for gene: LAMP3 was set to AMBER Added comment: PMID 40023045 reports a proband from one family with bi‑allelic loss‑of‑function LAMP3 variants causing childhood interstitial lung disease, and references three additional unrelated families (total 4 families, ≥5 individuals) with similar chILD phenotypes but details on these are scant. Supportive mouse model published previously PMID 34161347. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.189 | IFIH1 |
Zornitza Stark gene: IFIH1 was added gene: IFIH1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: IFIH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: IFIH1 were set to 37126154; 32508843 Phenotypes for gene: IFIH1 were set to Aicardi-Goutieres syndrome 7, MIM#615846 Review for gene: IFIH1 was set to AMBER Added comment: PMID 32508843 reports an individual with a heterozygous gain-of-function IFIH1 p.R779H variant causing Aicardi‑Goutières syndrome with interstitial lung disease, psoriasis and pulmonary hypertension; PMID 37126154 reports a second individual with a de novo heterozygous gain-of-function IFIH1 variant causing infantile lethal interstitial lung disease. This may be be a rare but significant manifestation of AGS. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.188 | IDUA | Zornitza Stark Marked gene: IDUA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.188 | IDUA | Zornitza Stark Gene: idua has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.188 | IDUA | Zornitza Stark Classified gene: IDUA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.188 | IDUA | Zornitza Stark Gene: idua has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.187 | IDUA |
Zornitza Stark gene: IDUA was added gene: IDUA was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IDUA were set to 37218880; 29654546 Phenotypes for gene: IDUA were set to Mucopolysaccharidosis type 1, MONDO:0001586 Review for gene: IDUA was set to GREEN Added comment: PMID 29654546 reports 2 individuals from 2 families and PMID 37218880 reports another individual, all with biallelic loss-of-function IDUA variants causing mucopolysaccharidosis type I (Hurler syndrome) presenting with neonatal interstitial lung disease, characterized by early respiratory failure and ground‑glass opacities. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.185 | IARS |
Zornitza Stark gene: IARS was added gene: IARS was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IARS were set to 40635052; 39950113 Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093 Review for gene: IARS was set to GREEN Added comment: PMID 39950113 reports an infant with biallelic IARS1 variants presenting with infantile pulmonary alveolar proteinosis, growth retardation, microcephaly, hypotonia, developmental delay and hepatopathy; PMID 40635052 reports 14 individuals from 14 unrelated families with biallelic IARS1 variants causing a recessive multisystem syndrome that includes pulmonary alveolar proteinosis in three families. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.183 | HMOX1 |
Zornitza Stark gene: HMOX1 was added gene: HMOX1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: HMOX1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HMOX1 were set to 38178812; 33066778 Phenotypes for gene: HMOX1 were set to Heme oxygenase-1 deficiency, MIM# 614034 Review for gene: HMOX1 was set to AMBER Added comment: PMID 33066778 and PMID 38178812 report 2 unrelated families (2 individuals) with biallelic HMOX1 loss‑of‑function variants presenting with childhood‑onset interstitial lung disease, hyperinflammation, haemophagocytic flares and multi‑system involvement. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.78 | WFDC2 |
Zornitza Stark gene: WFDC2 was added gene: WFDC2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: WFDC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WFDC2 were set to 38626355 Phenotypes for gene: WFDC2 were set to bronchiectasis, MONDO:0004822, WFDC2-related Review for gene: WFDC2 was set to GREEN Added comment: 11 individuals from 10 families reported with bi-allelic variants in this gene and bronchiectasis and nasal polyps. p.Cys49Arg is recurrent and may be a founder variant. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.49 | NAF1 |
Bryony Thompson gene: NAF1 was added gene: NAF1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: NAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NAF1 were set to 27510903 Phenotypes for gene: NAF1 were set to Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 Review for gene: NAF1 was set to GREEN Added comment: At least 3 probands/families with telomere-related pulmonary fibrosis and a supporting mouse model PMID: 27510903 - 5 individuals from 2 unrelated families with pulmonary fibrosis-emphysema and extrapulmonary manifestations including myelodysplastic syndrome and liver disease, with LoF variants. Truncated NAF1 was detected in cells derived from patients, and, in cells in which a frameshift mutation was introduced by genome editing telomerase RNA levels were reduced. Shortened telomere length also segregated with the variants. A Naf1+/- mouse model had reduced telomerase RNA levels ClinVar - 1 nonsense and 2 splice site variants (ID: 2443185, 1338525, 2443184) called LP by the Genetic Services Laboratory, University of Chicago but no clinical details were provided - SCV002547372.1 - Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center - at least one individual with pulmonary fibrosis and leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.39 | RPA1 |
Zornitza Stark gene: RPA1 was added gene: RPA1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Mode of inheritance for gene: RPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RPA1 were set to 34767620 Phenotypes for gene: RPA1 were set to Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres Mode of pathogenicity for gene: RPA1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: RPA1 was set to GREEN Added comment: 4 individuals with gain of function variants with bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopaenia, pulmonary fibrosis, or skin manifestations reported. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.32 | AFF4 |
Zornitza Stark gene: AFF4 was added gene: AFF4 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Mode of inheritance for gene: AFF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AFF4 were set to 31058441; 25730767 Phenotypes for gene: AFF4 were set to CHOPS syndrome, MIM# 616368 Review for gene: AFF4 was set to GREEN Added comment: Chronic interstitial lung disease is a feature of this condition. More than 15 unrelated individuals reported. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.30 | FLNA |
Zornitza Stark gene: FLNA was added gene: FLNA was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: FLNA were set to 30547349 Phenotypes for gene: FLNA were set to Interstitial lung disease Review for gene: FLNA was set to GREEN Added comment: Variants in FLNA cause a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, and intellectual disability. PMID 30547349 reviews 18 individuals with significant interstitial lung disease +/- other cardiac/neurological features. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.28 | ARHGAP42 |
Zornitza Stark gene: ARHGAP42 was added gene: ARHGAP42 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: ARHGAP42 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARHGAP42 were set to 34232960 Review for gene: ARHGAP42 was set to RED Added comment: Single individual reported with homozygous LoF variant, chILD disorder, systemic hypertension, and immunological findings. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.26 | OAS1 |
Zornitza Stark gene: OAS1 was added gene: OAS1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: OAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: OAS1 were set to 34145065; 29455859 Phenotypes for gene: OAS1 were set to Autoinflammatory immunodeficiency; infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinaemia Mode of pathogenicity for gene: OAS1 was set to Other Review for gene: OAS1 was set to GREEN Added comment: PMID 34145065:6 individuals reported with four different GoF variants and a polymorphic autoinflammatory immunodeficiency characterized by recurrent fever, dermatitis, inflammatory bowel disease, pulmonary alveolar proteinosis, and hypogammaglobulinaemia. PMID 29455859: Five individuals from three unrelated families including 3 sibs where the variant was present at mosaic level in one parent. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.12 | FARSA |
Zornitza Stark gene: FARSA was added gene: FARSA was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: FARSA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FARSA were set to 31355908 Phenotypes for gene: FARSA were set to Rajab interstitial lung disease with brain calcifications 2 619013 Review for gene: FARSA was set to RED Added comment: Autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts. Single affected individual reported, but FARSA interacts with FARSB, which causes a similar disorder. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.10 | TMEM173 |
Zornitza Stark gene: TMEM173 was added gene: TMEM173 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Mode of inheritance for gene: TMEM173 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM173 were set to 27613991; 32398023 Phenotypes for gene: TMEM173 were set to STING-associated vasculopathy, infantile-onset, MIM# 615934 Review for gene: TMEM173 was set to GREEN Added comment: Four individuals reported with severe interstitial lung disease in the setting of STING-associated vasculopathy. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||